tbuckley/cabot-search huggingface dataset:
Pulmonary Lymphoproliferative Disorders
Authors: Sergio Pina-Oviedo, Girish S. Shroff, Chad D. Strange, Jitesh Ahuja, Bradley S. Sabloff, Labib Gilles Debiane, Angel Rolando Peralta, Avi Cohen, Michael J. Simoff, Vishisht Mehta, Javier Diaz-Mendoza, William P. Brasher, Saadia A. Faiz, Patricia M. de Groot, Mylene T. Truong
Journal: Thorax (2023)

This chapter discusses the clinical, radiologic, histopathologic, and relevant cytogenetic and molecular alterations of reactive and malignant pulmonary lymphoproliferative disorders. All of these entities are rare—particularly when confined to the lung—and can be challenging when not properly recognized by clinicians, radiologists, and pathologists. Benign pulmonary lymphoproliferative lesions likely originate from hyperplasia of the bronchial-associated lymphoid tissue (BALT) secondary to chronic inflammatory stimulus, immune dysregulation, or an autoimmune disorder, and they may present as interstitial lung infiltrates or a mass-forming lesion on imaging. Importantly, persistent stimulus of the BALT may result in progression to pulmonary lymphoma. Reactive lymphoproliferative disorders discussed here include nodular lymphoid hyperplasia, follicular bronchiolitis, diffuse lymphoid hyperplasia/lymphoid interstitial pneumonia, and IgG4-related lung disease. Although the distinction of these lesions from a lymphoproliferative disorder is usually straightforward in a surgical resection, the diagnosis may be difficult in small biopsies. In this instance, the use of ancillary studies is extremely helpful in arriving at the correct diagnosis. Malignant pulmonary hematolymphoid disorders discussed here include non-Hodgkin lymphomas (extranodal marginal zone lymphoma of the mucosa-associated lymphoid tissue (MALT), diffuse large B-cell lymphoma, intravascular large B-cell lymphoma, lymphomatoid granulomatosis, plasmacytoma, other small B-cell lymphomas, and some T-cell lymphomas), classic Hodgkin lymphoma, and acute leukemia/myeloid sarcoma. Along with the proper morphologic evaluation, the diagnosis of these neoplasms requires the use of ≥1 ancillary studies to arrive at the correct diagnosis, and most cases require cytogenetics, fluorescence in situ hybridization, and/or molecular analyses to identify potential prognostic or predictive markers. Histiocytic disorders of the lung are also discussed in this chapter.
Miscellaneous Conditions
Authors: Rodeo Abrencillo, Isabel C. Mira-Avendano, Rosa M. Estrada-Y-Martin, Diana Palacio, Gokhan Kuyumcu, Labib Gilles Debiane, Angel Rolando Peralta, Avi Cohen, Michael J. Simoff, Vishisht Mehta, Javier Diaz-Mendoza, Patricia M. de Groot, Mylene T. Truong, Cesar A. Moran
Journal: Thorax (2023)

Miscellaneous conditions include Hermansky-Pudlak syndrome (HPS), Niemann-Pick (NP) and Gaucher diseases, dyskeratosis congenita (DC), pulmonary alveolar microlithiasis (PAM), pulmonary alveolar proteinosis (PAP), pulmonary hyalinizing granuloma (PHG), and IgG4-sclerosing disease. HPS is a rare autosomal recessive disorder characterized by oculocutaneous albinism, bleeding diathesis, and granulomatous colitis. NP and Gaucher diseases are rare lysosomal storage disorders, inherited in an autosomal recessive manner, that result in accumulation of lipid compounds in various organs. NP disease is associated with acid sphingomyelinase deficiency and Gaucher disease with deficient activity of the lysosomal enzyme glucocerebrosidase. DC, a congenital disease associated with telomere-mediated disorders, is actually recognized as a syndrome of telomere shortening, characterized by manifestations in multiple organs with the highest morbidity and mortality related to failure of the bone marrow, lung, and liver. PAM is an autosomal recessive disorder characterized by intra-alveolar accumulation of calcium phosphate deposits, called microliths, as a result of the inability of type II alveolar epithelial cells to clear phosphorus ions from the alveolar space, leading to microlith or calcospherite formation in the extracellular fluid. PAP manifests with progressive dyspnea caused by the accumulation of surfactant in pulmonary alveoli due to either defect in surfactant clearance or abnormal production. Primary PAP can be classified as autoimmune (most common type, 90% of the cases) or hereditary. Secondary PAP is seen in multiple diseases that affect macrophage function in the alveoli. PHG is an unusual pathological condition of unknown etiology although it may have an autoimmune origin. In some cases, PHG may be also associated with similar histological conditions such as retroperitoneal fibrosis and sclerosing mediastinitis. IgG4-sclerosing disease appears to be part of a more systemic process with an increased production of IgG4.
Neuroendocrine Neoplasms
Authors: Chad D. Strange, Patricia M. de Groot, Mylene T. Truong, Cesar A. Moran
Journal: Thorax (2023)

Neuroendocrine neoplasms represent an important group of tumors; however, the histological characteristics of these neoplasms are similar regardless of the site of origin. It is well known that these neoplasms may occur virtually in any anatomical site; therefore, clinical and radiological information becomes an important tool in the assessment of these neoplasms. From the immunohistochemical point of view, all these neoplasms will show similar immunophenotype using the more conventional and daily neuroendocrine markers such as chromogranin, synaptophysin, and CD56. In some cases adding TTF-1, CDX-2 may aid in the assessment of primary versus metastatic disease. However, the most important element in assigning site of origin should be based on the overall information of clinical, radiological, and pathological characteristics. More specifically regarding thoracic neoplasm, these tumors can be either primary neoplasm of the lung or of the thymus. Therefore, the use of radiological information in the assessment plays a crucial role, as the histology alone cannot determine primary site.
Mesenchymal Tumors of the Mediastinum
Authors: David I. Suster, A. Craig Mackinnon, Jitesh Ahuja, Patricia M. de Groot, Mylene T. Truong
Journal: Thorax (2023)

Mesenchymal tumors of the mediastinum are relatively rare; however, almost all types of mesenchymal lesions have been reported in this anatomic compartment. This includes vascular tumors, fibroblastic/fibrohistiocytic tumors, neurogenic tumors, myogenic tumors, lipomatous tumors, bone and cartilaginous tumors, and other tumors of uncertain etiology or histogenesis. These tumors cover the spectrum from benign to malignant neoplasms. The anatomic division of the mediastinum into three compartments, anterior, middle, and posterior, is helpful in certain instances when approaching these tumors; for example, neurogenic tumors are known to preferentially arise in the posterior mediastinum. In most cases these tumors share similar histologic and molecular genetic alterations to their soft tissue counterparts. Clinically the tumors may behave in slightly different manner as these lesions may sometimes grow and displace thoracic structures before becoming symptomatic. The diagnosis of these tumors often requires clinical, radiologic, and histologic correlation and in many cases will require ancillary diagnostic testing to secure the diagnosis.
Biphasic Neoplasms of the Lung
Authors: Chad D. Strange, Jitesh Ahuja, Girish S. Shroff, Bradley S. Sabloff, Patricia M. de Groot, Mathieu Marcoux, Mylene T. Truong, Cesar A. Moran
Journal: Thorax (2023)

Lung tumors with two lines of differentiation—epithelial and mesenchymal—are unusual and probably represent no more than 2% of all primary neoplasms of the lung. The two forms of pulmonary blastoma—monophasic and biphasic—represent a spectrum of differentiation. It is not uncommon to identify cases of monophasic pulmonary blastoma in which the tumor is associated with another malignancy not of mesenchymal origin, which renders the tumor biphasic on a different nature. Biphasic blastomas have more tendency to show hemorrhage and necrosis. Histologically, the epithelial component associated with biphasic blastomas is similar to that described in the monophasic variant of blastoma. However, the epithelial component in these tumors shows more cellular atypia and easily identifiable mitotic figures. Biphasic pulmonary blastomas also show the presence of a mesenchymal component in the form of muscle differentiation, cartilage, bone, or an unclassified spindle cell sarcoma. Carcinosarcoma also contains malignant epithelial and mesenchymal components. More often, definitive classification of these tumors is accomplished after complete surgical resection. Radiological imaging plays an important role in defining the details of these tumors, while immunohistochemistry plays a minor role and it is often used to determine specific types of sarcomatous elements.
Iatrogenic Conditions
Authors: Diana Palacio, Usha Jayagurunathan, Girish S. Shroff, Patricia M. de Groot, Mylene T. Truong, Cesar A. Moran
Journal: Thorax (2023)

Over a thousand medications are known to have the potential to result in lung injury. The constant development of new pharmaceuticals capable of inducing lung damage has grown to a point where it is a challenge to update the information. Fortunately, a comprehensive catalog can be found in the International Database "Pneumotox" ( www.pneumotox.com ). In this initiative, the imaging characteristics and/or suspected substance can be thoroughly researched, including common and unusual manifestations. It is important to be aware of the medication groups most likely to be associated with lung injury: antineoplastic drugs, antirheumatic medications, antibiotics, nonsteroidal anti-inflammatory agents (NSAIDs), antipsychotics, and antiarrhythmics. In the oncologic setting, it is important to be familiar with the variety of treatment-related side effects to avoid misinterpretation as tumor progression and to ensure appropriate management. Treatment options include chemotherapy, targeted therapy, immunotherapy, and radiation therapy. While recent advances in high-precision radiation therapy techniques such as stereotactic body radiotherapy (SBRT), intensity-modulated radiotherapy (IMRT), and proton therapy (PT) have decreased the radiation dose to normal tissues during treatment, radiation-induced lung injury usually occurs to some degree.
Salivary Gland-Type Tumors of the Lung
Authors: Ala Eddin Sagar, Mohammed Salhab, Archan Shah, Chad D. Strange, Jitesh Ahuja, Girish S. Shroff, Bradley S. Sabloff, Patricia M. de Groot, Mylene T. Truong, Cesar A. Moran
Journal: Thorax (2023)

Primary salivary gland-type tumors of the lung (SGTL) are rare and presumed to arise from the mucosal glands of the trachea and proximal bronchi. SGTLs are frequently mistaken for non-small cell carcinomas, but their incidence, clinical behavior, and prognosis are distinctly different from more aggressive forms of non-small cell lung neoplasms. The more common histologic subtypes of SGTLs include mucoepidermoid carcinoma (MEC) and adenoid cystic carcinoma (ACC). However, other neoplasms such as mixed tumor, epithelial–myoepithelial carcinoma (EM), acinic cell carcinoma (ACC), clear cell hyalinizing carcinoma (CCC), and oncocytoma have also been described. Together, SGTLs account for 0.1–0.2% of all thoracic malignancies. SGTLs have morphologic and immunohistochemical profiles similar to their counterparts of head and neck salivary gland origin. Thus, definitive diagnosis requires careful clinical, radiologic, and pathologic correlation. The incidence and behavior of salivary gland tumor subtypes vary with the tissue of origin, with most salivary gland tumors of lung origin being malignant, whereas tumors originating from the head and neck are frequently benign. Considerable variations in the clinical, epidemiologic, and histopathologic features of salivary gland tumor subtypes of lung origin also exist. Except for MEC, which may appear in adults and children, SGTLs are primarily adult tumors with a peak incidence in the fifth and sixth decades. Risk factors in the development of SGTL have not been clearly established, although an association with tobacco exposure for some phenotypes has been suggested. There is no specific staging system for SGTL. Data regarding prognosis is limited; however, histological type, grade, tumor size, and surgical resectability appear to be important prognosticators. Many questions regarding the optimal surgical approach and the efficacy of adjuvant chemotherapy and radiation therapy remain unanswered.
Infectious Diseases That May Mimic Lung Cancer
Authors: Brandy J. McKelvy, Jose A. B. Araujo-Filho, Myrna C. B. Godoy, Patricia M. de Groot, Mylene T. Truong, Cesar A. Moran
Journal: Thorax (2023)

The myriad of infections which can be confused with lung cancer includes bacterial, mycobacterial, fungal, and parasitic infections. Infections can present in various ways. When considering an infectious etiology of a lung nodule or mass, it is important to consider the prevalence of the particular disease in question. This means one must know all the particular elements of a patient's history. One will need to know where the patient was born, raised, and currently resides as well as travel history. Regional variations may be important to understanding the possible infectious differential. Additional important history elements will be occupational and environmental exposures because these too may also produce lung abnormalities. When possible, knowing the duration the lesion has been present and the rate of growth can help narrow the differential diagnosis. Finally, it is vitally important to know the immune status of the patient; infections may have different radiologic presentations depending if a patient is immunocompetent versus immunocompromised.
Pathology of the Lung Allograft
Authors: Sakda Sathirareuangchai, Jose R. Torrealba
Journal: Thorax (2023)

Recent advances in immunosuppressive medications, clinical immunology, patient selection, and surgical techniques have improved the outcome of lung transplants as a group, yet the overall survival is still the lowest among all solid organ allografts. Pathology has played a primordial role in this process by the recognition and understanding of the multifactorial complications that may affect lung allografts and decrease both organ and patient survival. In this chapter, we present the latest understanding and classification of the most common complication of lung allografts, including primary allograft dysfunction, acute cellular vs. antibody-mediated rejection, obstructive vs. restrictive chronic allograft injury, chronic allograft vasculopathy, infections of the transplanted lung, and special topics that include recurrent diseases in the lung transplant and posttransplant lymphoproliferative disorders. Classifications followed the International Society of Heart and Lung Transplant guidelines for both cellular and antibody-mediated rejection. We also refer to selected articles published in the medical literature and mention, when appropriate, our own experience in dealing with lung allograft biopsies and resection specimens.
Normal Thymus
Authors: Chad D. Strange, Patricia M. de Groot, Mylene T. Truong, Cesar A. Moran
Journal: Thorax (2023)

Even though the mediastinum encompasses several different anatomic structures, including the esophagus, lymph nodes, and cardiovascular structures, the mediastinal organ covered in this section will be the thymic gland, which is of true mediastinal origin, unlike the other structures. Traditionally the mediastinum has been divided into the superior, anterior, middle, and posterior compartments, which has informed lists of tumors that more commonly originate from these different compartments. It also seems practical from the surgical and pathological point of view to separate the mediastinum along these lines. However, the radiological features of the various compartments may be more specific in terms of the boundaries between compartments. Therefore, before we embark on a discussion of the rich pathology of mediastinal tumors, it is crucial not only to define the normal radiological characteristics and demarcations of the mediastinum but also to become familiar with the normal aspects of the thymic gland in order to address both pathological features and immunohistochemical profiles of some tumors.
Pulmonary Vasculitides
Authors: Maryam Kaous, Lilit A. Sargsyan, Diana Palacio, Jennifer A. Febbo, Loren Ketai, Matthew D. Gilman, Patricia M. de Groot, Mylene T. Truong, Cesar A. Moran
Journal: Thorax (2023)

Vasculitides refer to a heterogeneous set of diseases that are characterized by inflammation of vessel walls that leads to vessel narrowing, necrosis, obliteration, and subsequently to tissue ischemia. Vasculitis can be primary or secondary to another disease entity and can range from affecting only one organ to being a multiorgan systemic disease. Primary vasculitides frequently have some pulmonary manifestations, which may be part of the initial presentation. Discovery of pulmonary artery aneurysms, multiple pulmonary infarcts, and diffuse alveolar hemorrhage should always raise the question of an undiagnosed vasculitis. Takayasu arteritis, also called aortic arch syndrome, middle aortic syndrome, occlusive thromboaortopathy, and nonspecific aortoarteritis, requires a high index of suspicion for an early accurate diagnosis. Giant cell arteritis (GCA) receives its name from its typical histologic pattern. Classically a medium- and large-vessel vasculitis, GCA can affect all vessels of the body but has a predilection for extracranial branches of the carotid artery. Behcet's disease is a systemic idiopathic vasculitis with recurrent episodes of acute inflammation in multiple organ systems. It is classified as a variable-vessel vasculitis as it can affect small, medium, and large vessels, both arteries and veins. Classically a medium-vessel vasculitis, polyarteritis nodosa is a systemic necrotizing vasculitis that can also affect small vessels. Necrotizing sarcoid granulomatosis is an exceedingly rare type of vasculitis that is usually confined to the lungs and is a diagnosis of exclusion. It is characterized by sarcoid-like granulomas, granulomatous vasculitis, and a variable amount of necrosis. Kawasaki Disease has been reported globally, but there's a strong geographic and ethnic predominance. The highest incidence is in Japan. The best-established prognostic factor for the most feared complication in those with Kawasaki, coronary artery aneurysms, is age of onset. Isolated pauci-immune capillaritis is a small-vessel vasculitis that is localized to the lung with no other clinical or serologic markers of a systemic disease.
Uncommon Tumors of the Lung
Authors: Cesar A. Moran, Patricia M. de Groot, Mylene T. Truong, Pushan P. Jani, Alexis Preston, Sarah A. Holevinski, Colin Zuchowski, Diana Palacio
Journal: Thorax (2023)

As its name implies, these are tumors belonging to different lineages and their occurrence in the lung is extremely rare. These tumors are more common in other anatomical areas outside of the thoracic cavity; however, in some cases, their occurrence in the lung may be due to ectopic tissues or vestiges of tissues during embryological development. This group of tumors includes both benign and malignant neoplasms. Because the occurrence of some of these tumors is more common in extra-thoracic areas, metastatic disease is important to consider and properly rule out. In other cases, small biopsies of the lung may not be sufficient to make an unequivocal interpretation, thus leaving the final interpretation to be made after complete surgical resection. Clinical and radiological information plays an important role not only in providing important past medical history but also in providing information about the location and singularity or multiplicity of the tumor. Immunohistochemical analysis of these tumors is essential in arriving a more specific diagnosis.
Genetics of Congenital Heart Disease
Authors: Akl C. Fahed, Bruce D. Gelb, J. G. Seidman, Christine E. Seidman
Journal: Circulation Research (2013)

Congenital heart disease (CHD) is the most common congenital anomaly in newborn babies. Cardiac malformations have been produced in multiple experimental animal models, by perturbing selected molecules that function in the developmental pathways involved in myocyte specification, differentiation, or cardiac morphogenesis. In contrast, the precise genetic, epigenetic, or environmental basis for these perturbations in humans remains poorly understood. Over the past few decades, researchers have tried to bridge this knowledge gap through conventional genome-wide analyses of rare Mendelian CHD families, and by sequencing candidate genes in CHD cohorts. Although yielding few, usually highly penetrant, disease gene mutations, these discoveries provided 3 notable insights. First, human CHD mutations impact a heterogeneous set of molecules that orchestrate cardiac development. Second, CHD mutations often alter gene/protein dosage. Third, identical pathogenic CHD mutations cause a variety of distinct malformations, implying that higher order interactions account for particular CHD phenotypes. The advent of contemporary genomic technologies including single nucleotide polymorphism arrays, next-generation sequencing, and copy number variant platforms are accelerating the discovery of genetic causes of CHD. Importantly, these approaches enable study of sporadic cases, the most common presentation of CHD. Emerging results from ongoing genomic efforts have validated earlier observations learned from the monogenic CHD families. In this review, we explore how continued use of these technologies and integration of systems biology is expected to expand our understanding of the genetic architecture of CHD.
Familial Associations of Prevalence and Cause-Specific Mortality for Thoracic Aortic Disease and Bicuspid Aortic Valve in a Large-Population Database
Authors: Jason P. Glotzbach, Heidi A. Hanson, Joseph E. Tonna, Joshua J. Horns, Chelsea McCarty Allen, Angela P. Presson, Claire L. Griffin, Megan Zak, Vikas Sharma, Martin Tristani-Firouzi, Craig H. Selzman
Journal: Circulation (2023)

Thoracic aortic disease and bicuspid aortic valve (BAV) likely have a heritable component, but large population-based studies are lacking. This study characterizes familial associations of thoracic aortic disease and BAV, as well as cardiovascular and aortic-specific mortality, among relatives of these individuals in a large-population database.
Moving toward structured, specialized hidradenitis suppurativa care to improve patient outcomes
Authors: Niamh Kearney, Brian Kirby
Journal: British Journal of Dermatology (2023)

Journal Article Corrected proof Moving toward structured, specialized hidradenitis suppurativa care to improve patient outcomes Get access Niamh Kearney, Niamh Kearney Department of Dermatology, Belfast Health and Social Care Trust, Belfast, UKSchool of Medicine, University College Dublin, Ireland Correspondence: Niamh Kearney. Email: nkearne@tcd.ie https://orcid.org/0000-0002-6469-3462 Search for other works by this author on: Oxford Academic Google Scholar Brian Kirby Brian Kirby School of Medicine, University College Dublin, Ireland Department of Dermatology, St. Vincent’s University Hospital, Dublin, IrelandCharles Institute of Dermatology, University College Dublin, Ireland https://orcid.org/0000-0001-7596-892X Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljad198, https://doi.org/10.1093/bjd/ljad198 Published: 15 June 2023 Article history Received: 07 June 2023 Accepted: 10 June 2023 Published: 15 June 2023 Corrected and typeset: 26 July 2023
International Atherosclerosis Society guidance for implementing best practice in the care of familial hypercholesterolaemia
Authors: Gerald F. Watts, Samuel S. Gidding, Robert A. Hegele, Frederick J. Raal, Amy C. Sturm, Laney K. Jones, Mitchell N. Sarkies, Khalid Al-Rasadi, Dirk J. Blom, Magdalena Daccord, Sarah D. de Ferranti, Emanuela Folco, Peter Libby, Pedro Mata, Hapizah M. Nawawi, Uma Ramaswami, Kausik K. Ray, Claudia Stefanutti, Shizuya Yamashita, Jing Pang, Gilbert R. Thompson, Raul D. Santos
Journal: Nature Reviews Cardiology (2023)